HIMAC

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HIMAC

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Cancer Treatment by Charged Particles

- Carbon Ion Radiotherapy – Part 1

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Takeshi Murakami Research Center of Charged Particle Therapy

National Institute of Radiological Sciences

2012.07.04-5

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Site of NIRS

Chiba Prefecture

Narita

airport

Tokyo

National Institute of

Radiological Sciences

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HIMAC

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Introduction to National Institute of Radiological Sciences (NIRS)

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History of NIRS

In these days, • A series of nuclear weapons tests, above-ground level, in

Cold War era, • Memory of tragedies at Hiroshima and Nagasaki, • Daigo Fukuryū Maru accident in 1954,

• A Japanese fishing boat, Daigo Fukuryū Maru ("Lucky Dragon

No. 5"), came in direct contact with the fallout from a

thermonuclear hydrogen bomb (Castle Bravo )near Bikini atoll.

NIRS was founded in 1957.

Creating concerns about radiation for Japanese citizens.

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Objectives of NIRS

Studies for Adverse Effects

of Radiation on Humans

and the Environment

- Protection, Diagnosis,

and Treatment

Medical Applications

of Radiation

Radiation Therapy

Medical Imaging

Education and Training

of Human Resources

Positive side

Countermeasures of

Accidental

Radiation Emergency

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HIMAC

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Organization

Dept. of Planning and Management

Dept. of General Affairs

Research, Development and Support Center

Research Center for Charged Particle Therapy

Molecular Imaging Center

Research Center for Radiation Emergency Medicine

Research Center for Radiation Protection

Staff: 814

-full time: 490

-part time: 324

Audit Office

International Open Laboratory

Medical Exposure Research Project

Research, Development and Support Center

Supporting four research centers in technology, maintaining

circumstances safe and suitable for research and training /education of

human resources

Research Centers

Research Center

for Charged Particle

Therapy

- Charged Particle

Cancer Therapy -

Molecular Imaging

Center

- Molecular Imaging

for diagnosing

Cancer, etc

Research Center

for Radiation

Protection

- Low Dose Radiation

effects on Humans

and Environment -

Research Center for

Radiation

Emergency

Medicine

- Radiation Emergency

Medicine and research of high

dose radiation

effect on humans -

Heavy Ion Radiation Therapy

Production of Molecular

Markers with Cyclotrons

PET Imaging of a Brain Study on biology effect

and environmental effect

Dose estimation due to

man-made radiation and

environmental radiation

Formation of Radiation

Emergency Medicine

Regional Level

Local Hospitals

Supporting and

developing technologies

Safety

and

Security

Training

and

Education

NIRS

B Prefecture D Prefecture

C Prefecture A Prefecture

Radiation Emergency Medicine

Network

Choromo-some Network

Physical

Dosimetry

Network

Western

Japan

Hiroshima Univ. NIRS

Eastern

Japan

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Global cancer facts and figures

Cancer is the leading cause of death in developed countries and the second leading cause of death in developing countries.

American

cancer society

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Treatments of cancer

1. Surgery

2. Chemotherapy

3. Radiotherapy

Advantage: no pain, no infection

Kinds of radiation

• X-rays

(particle beams)

• Protons

• Carbon beams

Expectation and concern on radiation therapy

Quality Of Life after the treatment (QOL)

malignant, radiation resistant tumor

Fractionation

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Feature of the Charged Particle Therapy Physics

Dose distribution

Heavy ions, Protons

• Surface = small LET

• End point = large LET

Dose concentrates at the end point

(Bragg peak)

Gamma-ray, Neutrons

• from Surface to End point = constant LET

(LET：Lenear Energy Transfer)

0

20

40

60

80

100

0 5 10 15

Depth in water (cm)

Rela

tive d

ose (

%)

C ion

n

gamma-ray

proton

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Dose distribution of x-rays and C beams

tumor tumor

Bolus

3 directions

Carbon beams X-ray

9 directions

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Heavy Ions and Protons

Scattering effect (transverse)

Heavy ion -> small

(Solid line)

Proton -> large

(Dotted line)

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Ionization density and damage of DNA

-2.5

0.0

2.5

20 22 24 26 28 30

X (n

m)

Z (nm)

-2.5

0.0

2.5

0 2 4 6 8 10

X (n

m)

Z (nm)

-2.5

0.0

2.5

0 2 4 6 8 10

X (n

m)

Z (nm)

DNA

Truck structure Lethal damage

X-rays

Protons

Carbons

1.1

1.0

2~3

RBE

2 nm

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Survival curve

low LET

X-ray, C:13keV/μm

Middle LET

C:30keV/μm

high LET

C:110keV/μm 0.01

0.1

1

0 5 10 15

X-ray133060110152237生

存

率

線量 (Gy)Dose (Gy)

Su

rviv

al ra

te

by Y. Furusawa (NIRS)

RBE=𝐷𝐿

𝐷𝐻

DL

DH

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Feature of the Heavy Ion Therapy Biology

Biological effectiveness

Heavy Ion Beam = High LET

Large RBE

（RBE：Relative Biological

Effectiveness)

Low OER

(OER:Oxygen Enhancement Ratio)

　 RBE and OER dependence on

LET

0

1

2

3

4

1 10 100 1000 10000

LET∞（ keV/μ）R

BE

, O

ER

RBEOERHCSi

Ｃ Ｈ Ｓｉ

(keV/μm)

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0.0001

0.001

0.01

0.1

1

0 5 10 15 20 25 30 35

Su

rviv

ng

fra

cti

on

Dose (Gy)

γ-ray

Hypoxic

Oxic 0.001

0.01

0.1

1

0 5 10 15 20 25 30 35

Su

rviv

ing

fra

cti

on

Dose (GyE)

carbon

74 keV/ μm

74 keV/ μm

Oxygen effect

γ-ray Carbon

hypoxic

oxic

Ando et al. Int J Radiat Biol 1999

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Result of clinical trials

Head & Neck cancer

(before / treatment planning / after)

before 36 month after

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Keywords, Procedures and judgments

1. Protocol

– A predetermined plan for carrying out treatments

– Phase I: Adverse effect? -> Phase II: Dose escalation

2. How doctors decide success or not for cancer treatment?

– What should be observed?

– Local control

– 5-year (3-year) survival

3. Fractionation

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NIRS Number of patients enrolled for carbon ion radiotherapy

from June 1994 to February 2012

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Number of patients, yearly base

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Highlight of Carbon Ion Radiotherapy

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Requirements for the therapy at HIMAC

- Ion species: high LET (100keV/mm) charged particles

He, C, Ne, Si

- Range: 30cm in soft tissue 430MeV/u (C)

800MeV/u(Si)

- Maximum irradiation area: 22cm in diameter

- Dose rate: 5GyE/min 2×109pps

- Beam direction: horizontal, vertical, etc...

-> “large accelerator” used for physics experiments

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History of constructing HIMAC

Heavy Ion Medical Accelerator in Chiba (HIMAC) 1984: 10 years strategy for confronting the cancer 1986: International Workshop on Heavy Ion Treatment

Facility 1989: Start of the construction 1993: Commissioning ended, beams were successfully

accelerated. 1994: Clinical Trials began. 2003: Advanced Medicine (Advanced Medical Therapy). - June. 2012: 6,512 patients were treated. (AM 3,488)

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Bird’s eye view of HIMAC and hospital

HIMAC Hospital

Offices

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Devices of HIMAC

HIMAC

(Heavy Ion Medical Accelerator in Chiba)

130m

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HIMAC

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Devices of HIMAC

HIMAC

(Heavy Ion Medical Accelerator in Chiba)

130m

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HIMAC

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Devices of HIMAC

HIMAC

(Heavy Ion Medical Accelerator in Chiba)

130m

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Irradiation method

Beams from the accelerator

≠ beams for treatment

í Large area

• Uniform field

í Large thickness

Making of SOBP

(Spread Out Bragg Peak)

• Physical dose distribution consists of

many Bragg peaks with various range

• Biological equivalent dose

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Beam Delivery System

Wobbling Magnet

Multi Leaf Collimator

Bolus Collimator

Ridge Filter

Range Shifter Cancer Tumor Irradiation area

Scattering material

Controller

Dose monitor

Making of Spread Out Bragg Peak

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Irradiation system of coincident with a patient‘s respiratory motion

Irradiation room

Positioning area

Accelerator Treatment control

Gate signal generator

Watch & record system

Beam monitor

Planning

simulation Reference Image

Positioning system

using x-ray TV images

Compare

X-ray TV

Positioning Image

PSD

Respiration

waveform

Gated beam extraction system

(RF knockout method)

Interlock system

Ion beam

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End-expiratory irradiation

Respiration gating for irradiation

Reduction of volume

Minohara et al. IJROBP 47:1097-1103, 2000

No gating Gating

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Key Tech in C-ion RT at HIMAC

Respiration gating: 3089 patients

lung, liver, pancreas, kidney, sarcoma etc

Patch field : 294 patients

Head & Neck, para-spinal etc.

Spacer insertion :108 patients

pelvis and abdomen

32

More than 3000 patients were treated

with these techniques at NIRS.

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Classification of shielding and activation

Radiation shielding

• Fast neutrons

• Gamma rays -> negligible small

Devices irradiated by beams

-> Accelerator and irradiation system

• Beam stoppers, beam monitors, deflector, septum

magnets, targets used in basic research

• Dose monitor, ridge filter, range shifter, multi-leaf

collimator, bolus collimator, patient collimator

• Air

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Induced activity

Not irradiated by beams : neutron captures?

-> Devices and buildings

• Vacuum ducts, magnets

• Neutron shutters

• Building material, concrete etc.

• Cooling water for devices

• Underground water

• Air

No radioisotopes for treatment

• PET -> Diagnosis only (not in the HIMAC building)

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Regulation in Japan

(Japanese laws: based on ICRP standards.)

Irradiation rooms, accelerator rooms: no entry while beam is on.

Regulations related to accelerators.

Area 1: 1 mSv/week

Controlled area. Registered workers can enter all the

time.

Area 2: 1.3 mSv/3 months

Border of a controlled area.

Area 3: 250 μ Sv/3 months

Border of an institute’s site.

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Thickness of the wall - fast neutrons -

Thickness of the shielding wall

->Equations of Hirayama & Ban ->Numerical simulation

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Design of treatment rooms

11hs/w

11hs/w

18hs/w

door: 10cm

Polyethylene

Effe. 395cm

(concrete + iron)

Periodic

measurements:

2/year

Multi-legged

chicane

Neutron monitor

Display

Effe. 317cm

(250cm concrete

+ 30cm iron)

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Devices irradiated by beams

495μSv/h

14μSv/h at 1m

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Devices irradiated by beams -2

<10μSv/h at 1m

Mostly <1μSv/h

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Measured: Exhaust (FY2006)

ガスモニター

0.00E+00

5.00E-03

1.00E-02

1.50E-02

2.00E-02

2.50E-02

3.00E-02

3.50E-02

4.00E-02

4.50E-02

5.00E-02

2006/4/1 2006/6/30 2006/9/28 2006/12/27 2007/3/27

Air

average

max.

Detection limit

Machines not

working

Bq/cc

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Measured: water (FY2003)

water

0.00E+00

1.00E-02

2.00E-02

3.00E-02

4.00E-02

5.00E-02

6.00E-02

2002/12/10

2003/3/20

2003/6/28

2003/10/6

2004/1/14

2004/4/23

1.00E+00

1.00E+01

1.00E+02

1.00E+03

濃度比

放流量(m3)

Ratio

Released

(m3)

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Summary of the safety issue

Medical accelerator for cancer treatment

fast neutrons -> needs careful design!

activation by beams -> very small, safe, but needs

careful handling

• Use plastic, not metal, if possible

• (small activation, short life)

induced activity : no problem!

• High energy but low intensity, short irradiation time

• Beam intensity : HIMAC -> ～10^9 pps <nA

• RI production -> ～ 10 μA

• 70 patients x 5 min = 350 min + cond. + meas. /day 3rooms